Since 1989, I have participated in several research projects in the immunology laboratory of Dr. Abul Abbas at the Brigham and Women's Hospital. In this laboratory, the characteristics of murine helper T cell subsets were examined, along with their modes of activation and differentiation. In one set of experiments, we found that different helper T cell clones responded differently depending on the type of antigen presenting cell (APC) present. When Th2 clones, which produce IL-4 and IL-S and are important in IgE -and eosinophil-mediate reactions, were stimulated with antigen (Ag) and purified B cells, the T cells did not respond maximally, either b proliferation or by IL-4 secretion, unless IL-I was added to the culture or macrophages, a strong producer of IL-1, were used as the APCs instead of B cells. Thl clones, which produce IL-2 and IFNg and induce macrophag activation and cell-mediated immunity, responded maximally, as measured by proliferation and cytokin production, when either macrophages or B cells were used. Thus, IL-1 is an important costimulator for the expansion of Th2 clones while Thl clones are neither responsive to nor dependent on IL-1. In another set of experiments, selective unresponsiveness to Ag was induced in Thl but not Th2 cells in vivo. When mice were pretreated with haptenated TNP-conjugated soluble antigen and then immunized with Ag + adjuvant, the harvested T cells showed no proliferation and reduced cytokine secretion of IL-2 and IFNg but no reduction in IL-4 when stimulated with Ag in vitro. Serum antibody revealed reduced IgG2a and IgG2b which are produced by B cells upon IFNg-induced switching, but normal amounts of IgE and IgG1 which are produced upon IL-4 switching. Naive CD4+ T cells differentiate into different effector subsets based on the type of cytokines and APC, present during initial activation. Using a transgenic mouse model, an experimental system was developed where normal naive T cells were induced to differentiate into Thl and Th2 subsets by APC-dependent stimulation using superantigen presented by Class II MHC. The results revealed that IL-4 added to the primary culture caused the expansion of Th2-like IL-4 producers, especially when the APCs were B cells; IL-1 receptor antagonist did not inhibit the production of IL-4-producing cells; IL- 10 inhibited the differentiation of T cells into effectors when th APCs were macrophages/dendritic cells but not when the APCs were B cells; IFNg inhibited IL-4 producers; and IL-4-producing T cells were the most potent helpers for B cells. Costimulation is essential for Ag-induced IL-2 production by Th1 cells but not for IL-4 production by Th2 cells. IL-2 production by CD4+ T cells from transgenic mice specific for cytochrome c requires the presence of either intact APCs or chemically-inactivated APCs with the addition of anti-CD28 to mimic costimulation. IL-4 production, however, required no anti-CD28. Costimulator independence of IL-4 secretion suggests that Th2 cells may be preferentially activated by tissue antigens presented by costimulator-deficient APCs.